We propose to conduct a prospective, pooled analysis of the association between circulating 25- hydroxyvitamin D [25(OH)D] levels and risk of breast and colorectal cancer within a consortium of 15 cohort studies. We hypothesize that higher levels of circulating 25(OH)D levels are associated with a reduced risk of colorectal and breast cancer. These associations are hypothesized to be stronger among leaner individuals, among more physically active individuals, and among individuals with higher calcium intakes. Inclusion criteria for participation in the consortium are that a study used a prospective study design, collected blood samples prospectively, and had at least 50 cases of the specific cancer being analyzed. The 15 studies in the consortium were conducted in North America (n=10), Europe (n=4), and Asia (n=1) and include 5061 colorectal cancer cases and 6817 breast cancer cases whose circulating 25(OH)D levels have been measured previously or will be measured (mostly as part of this proposal). We will analyze the primary data from each study so that circulating 25(OH)D levels and confounding variables will be modeled consistently across studies. This will reduce potential sources of between-studies heterogeneity due to different analytic approaches as encountered in the published literature, as well as allow for examination of different categorizations of circulating 25(OH)D levels. We also will be able to evaluate whether associations vary among population subgroups, by other biochemical risk factors, and by tumor subtypes which cannot be evaluated fully in a meta-analysis of the published literature. Further, new data will be generated in seven of the studies which will reduce the influence of publication bias. This proposal takes full advantage of extensive data collected throughout the world, builds upon the expertise and established collaboration of the investigators, and takes advantage of the statistical power of the project. These analyses will provide powerful insights into the relation between vitamin D and breast and colorectal cancer risk. The results have the potential to inform recommendations regarding sun exposure and vitamin D intake requirements, and contribute to the reduction of the burden of cancer. PUBLIC HEALTH RELEVANCE: Confirming whether vitamin D reduces the risk of breast and colorectal cancer, two of the most common cancers in the United States, is critical because current health recommendations typically do not encourage intakes of vitamin D high enough to appreciably influence 25(OH)D levels and they tend to discourage sun exposure because of the risk of skin cancer and melanoma.